Primary failure of eruption and other eruption disorders—Considerations for management by the orthodontist and oral surgeon Sylvia A. Frazier-Bowers, Sonny Long, and Myron Tucker Tooth eruption is a highly variable process, and the disorders that stem from a defective eruption process are often difficult to diagnose. The eruption process can range from normally timed and sequenced events to one characterized by eruption delays or a primary failure of eruption (PFE, OMIM 125350)—with partially or completely unerupted teeth in the absence of a mechanical obstruction. Our understanding of the molecular basis of tooth eruption was drastically strengthened when one gene, parathyroid hormone receptor 1 (PTH1R), was found to be causative for familial cases of PFE. Although PFE is a relatively rare condition, knowledge of a biological mechanism underlying the development of PFE illuminates: (1) the influence of genetics on orthodontic tooth movement in general; (2) the differential diagnosis of clinical eruption disorders; and (3) the correlation of a biologic basis with the clinical manage- ment of eruption failure. In this article, we consider the best clinical manage- ment of eruption disorders from the standpoint of what is known from a biological perspective about normal tooth eruption and therefore eruption disorders. Specifically, how the diagnosis influences the clinical management of eruption disorders using biologic versus clinical factors is considered. These advances in our understanding of normal and abnormal tooth eruption now allow for a systematic clinical diagnostic regime that may include a surgical approach or simply the elimination of treatment with a continuous archwire. (Semin Orthod 2015; ]:]]]–]]].) & 2015 Elsevier Inc. All rights reserved. Introduction D iagnosis and clinical management of eruption disorders can be quite challeng- ing. The critical features of diagnosis can be broken into several major categories, including syndromic versus isolated, genetic versus envi- ronmental, and of course idiopathic. Primary failure of eruption (PFE, OMIM #125350), originally described by Proffit and Vig, 1 is characterized by eruption failure of permanent teeth in the absence of mechanical obstruction or syndrome. The hallmark features of this condition are: 1. Infraocclusion of affected teeth. 2. Significant posterior openbite malocclusion accompanying normal vertical facial growth. 3. The inability to move affected teeth orthodontically. Many historic studies have noted the heritable basis of infraoccluded teeth or eruption dis- orders. 2–7 Until the reports of mutations in the parathyroid hormone receptor 1 gene (PTH1R), non-syndromic eruption disturbances (i.e., anky- losis, secondary retention, primary retention, and PFE) were difficult to distinguish from one & 2015 Elsevier Inc. All rights reserved. 1073-8746/12/1801-$30.00/0 http://dx.doi.org/10.1053/j.sodo.2015.10.006 We gratefully acknowledge the support of the families and dentists whose participation in our studies contributed to this article. The research was supported by NIH, United States, Grants 1K23RR17442 and M01RR-00046. Department of Orthodontics, University of North Carolina, School of Dentistry, Chapel Hill, NC; Department of Pediatric Dentistry, University of North Carolina, School of Dentistry, Chapel Hill, NC and Private Practice in Orthodontics and Pediatric dentistry, Charlotte, NC; Department of Oral and Maxillofacial Surgery, Louisiana State University School of Dentistry, Oral and Max- illofacial Surgery Educations Services Consultant, Isle of Palms, SC. Address correspondence to Sylvia A. Frazier-Bowers, DDS, PhD, Department of Orthodontics, University of North Carolina, School of Dentistry, Chapel Hill, NC 27599. E-mail: sylvia_frazier-bower- s@unc.edu 1 Seminars in Orthodontics, Vol ], No ] (), 2015: pp ]]]–]]]